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The following message was posted to: PharmPK
I am looking for a formula for estimating t1/2 in human based on known
t1/2 in rats. Does anyone have one handy?
Thanks,
James
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The following message was posted to: PharmPK
James Pan asks:
I am looking for a formula for estimating t1/2 in human based on
known
t1/2 in rats. Does anyone have one handy?
If only it were that simple. There is no easy answer to your question.
You can try allometric scaling clearance and volume of distribution
(Vz) and then use the halflife equation, but it has been my experience
that this rarely works. In general, animals have faster half-lives
than humans so you may want to treat the animal half-life as a lower
bound. Maybe someone else has some other suggestions.
Peter Bonate
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James,
one of many possible formulas is:
log10[half-life in human]=0.906*log10[half-life in rat]+0.723
where log10 is logarithm using base 10.
the full reference is
RS Obach, JG Baxter, TE Liston, BM Silber, BC Jones, F MacIntyre, DJ
Rance, and P Wastall
The prediction of human pharmacokinetic parameters from preclinical and
in vitro metabolism data.
J. Pharmacol. Exp. Ther., Oct 1997; 283(1): 46-58.
this is free full text article at
http://jpet.aspetjournals.org/cgi/reprint/283/1/46.pdf
Regards
Dr Stefano Porzio
Pharmacokinetic & Tox. Dept.
Inpharzam Ricerche SA
Zambon Group
PO Box 328 - Via ai Söi
CH-6807 Taverne
Switzerland
[This approach would have best success with high fe drugs, extensive
metabolism could mean species specific metabolism - db]
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The following message was posted to: PharmPK
Dear Dr. Porzio,
With respect to the equation for estimating t1/2 in man using rat data:
Please add the unit of time of this equation, because it is
unit-sensitive,
and can be valid only for one particular unit of time (probably hours?).
An interesting aspect is that the difference between man and rat, when
expressed as the ratio t1/2_man / t1/2_rat, decreases with increasing
half-life. Example:
t1/2_rat t1/2_man t1/2_man / t1/2_rat
1 5.28 5.28
10 42.6 4.26
100 343 3.43
Intuitively, the declining ratio makes sense, but I cannot give strong
arguments for this.
Using the usual allometric scaling on clearance proportional to BW^0.75
and
volume of distribution proportional to BW, would provide an allometric
scaling for half-life proportional to BW^0.25. For a rat of 250 g and a
man
of 70 kg, this yields a ratio of (70/0.25)^0.25 = 4.09. This value is
indeed
within the range in the above example, but this value is independent of
t1/2.
It would be interesting to hear comments and experiences of others on
this
topic.
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.aaa.farm.rug.nl
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)